IN THE COURT OF THE COMMISSIONER OF PATENTS FOR 
THE REPUBLIC OF SOUTH AFRICA

CASE NO: SA Patent no. 96/3472
DATE: 14/04/2010

In the matter between:

And

MOLOPA-SETHOSA J

The Applicants launched this application for the amendment of South African Patent No. 96/3472 ("the patent") in terms of section 51(9) of The Patents Act 57 of 1978 ("The Act"). The applicants are the registered patentees of the patent herein.

1.	The use of amoxycillin trihydrate and potassium clavulanate in combination in a weight ratio of between 6:1 and 8:1 (the weights being expressed as the free parent acids amoxycillin and clavulanic
acid), in the manufacture of a medicament for treating bacterial infections in paediatric patients which medicament is administered twice daily (bid), at a dosage of between 20 and 70mg/kg/day of
amoxycillin and pro rata amounts of clavulanic acid.

3. A use as claimed in claim 1 or 2 in which the weight ratio is from 6.5:1 to 7.5:1.
4. A use as claimed in any one of the claims 1 to 3 in which the weight ratio is about 7:1.
5. A use as claimed in any one of claim 1 to 4 which the dosage regimen is 70 ~ 10%mgfkg/day amoxycillin in combination with 10+-10%mg/kg/day clavulanic acid.

7. A use as claimed in any one of claims 1 to 10 in which the dosage regiment is 35+-10%mg/kg/day amoxycillin in combination with 5+-10mg/kg/day clavulanic acid.
8. A use as claimed in any one of the claims 1 to 10 in which the formulation is provided as a liquid aqueous suspension.
9. A pharmaceutical formulation adapted for paediatric oral bid administration, comprising amoxycillin trihydrate and potassium clavulanate in combination, in a weight ratio of between 6:1 and 8:1 (the weights being expressed as the free parent acids amoxycillin and clavulanic acid) and which, when reconstituted, comprises amoxycillin in an amount of from 150 to 450mg/5ml of liquid aqueous suspension and clavulanic acid in an amount of from 25 to 75mg/5ml of liquid aqueous suspension.
10. A formulation as claimed in claim 9 comprising amoxycillin and clavulanic acid in combination, in a weight ratio of between 6.5:1 and 7.5:1.
11. A formulation as claimed in claim 9 comprising amoxycillin and clavulanic acid in combination, in a weight ratio of 7:1.
12. A formulation as claimed in any one of the claims 9 to 11 in the form of a dry powder or a granule formulation for reconstitution into a suspension with water or other suitable aqueous media to form a suspension formulation.
13. A formulation as claimed in any one of claims 9 to 11 in the form of a liquid aqueous preparation.
14. A formulation as claimed in any one of claims 9 to 13 provided for administration at a dosage of from 20 to 70mg/kg/day of amoxycillin.
15. A formulation as claimed in claim 14 provided for administration at a dosage of from 40 to 70mg/kg/day of amoxycillin.
16. A formulation as claimed in claim 9 provided for administration at a dosage of 45+-10%mg/kg/day amoxicillin and 6.4+-10%mg/kg/day clavulanic acid.
17. A formulation as claimed in 9 provided for administration at a dosage of70+-10%mg/kg/day amoxycillin and 10+-10%mg/kg/day clavulanic acid.
18. A formulation as claimed in claim 15 provided for administration at a dosage of 35+-10%mg/kg/day amoxycillin and 5+-10%mg/kg/day clavulanic acid.
19. A formulation as claimed in any one of claims 9 to 18 provided for administration in units doses of quantities amoxycillin and clavulanic acid corresponding to amoxycillin: clavulanic acid ratio of200+-10% : 28.5+-10% and400+-10% : 57+-10% mg/5ml
20. A formulation as claimed in any of claims 9 to 19 in which the proportion of amoxycillin and clavulanic acid is from 35-60 wt%, in a dry formulation for make up with aqueous media into a suspension formulation.
21. A formulation as claimed in any one of claims 9 to 20 which is substantially free of mannitol.
22. A pharmaceutical formulation adapted for reconstitution as a liquid aqueous suspension comprising amoxycillin trihydrate and potassium clavulanate and which, when reconstituted, comprises amoxycillin in an amount 200+-10% and clavulanic acid in an amount 28.5+-10% or amoxycillin in an amount 400+-10% and clavulanic acid in an amount 57+-10%mg/5ml of liquid aqueous suspension.
23. A formulation as claimed in claim 9 having a composition within +-10% of the formulae listed below, expressed as mg/5ml dose of reconstituted aqueous suspension:

Ingredient	mg/5ml	mg/5ml
Amoxycillin trihydrate	408.0
204.0
Potassium clavulanate	61.56
39.78
Xanthan gum	12.5	12.5
Colloidal silica	25.0	25.0
Succinnic acid	0.84	0.84
Orange flavour	15.0
15.0
Orange flavour	11.25	11.25
Golden syrup flavour	23.75	23.75
Aspartame	12.5
12.5
Hydroxypropylmethyledellulose	79.65
79.65
Silicon dioxide	to 885.5	to 537.5
24. A pharmaceutical formulation as claimed in any one of claims 9 to 23 for use in therapy.
25. A process for manufacturing a formulation according to any one of claims 9 to 23 comprising the step of mixing dry powder or granulated ingredients for loading into a suitable container. "

The applicants contend that the combination of amoxycillin and potassium clavulanate is an extremely famous and widely used oral medicament for bacterial infections marketed by the patentees' predecessors in title under the famous trade mark AUGMENTIN.

On 27 January 2006. the respondents filed an application for the revocation of the patent. This, amongst others, inspired the applicants to apply to amend the claims of the patent. The application to amend is dated 17 May 2006.

The amendment is opposed by the respondents.

By agreement between the parties the revocation application (prayer (b) of the notice of motion), is stayed pending the outcome of the amendment application.

At the commencement of the proceedings counsel for the applicants indicated that although they (applicants) had filed an application to strike out some of the paragraphs of the affidavit of one Lynton Hilliard-Lomas ("Lomas"), the applicants were not going to persist in that application.

be ordered to pay the costs up to the time they filed their replying affidavit.

The applicants* reasons for making the amendment are described as follows:

6.1 The patentees are aware that there has been some debate as to the validity of corresponding foreign patents and patent applications, notably in Australia, New Zealand, Eurasia, Romania, United States, and the European Patent Office. No final decisions as to the validity of the claims of the two European applications have as yet been taken.
6.2 Earlier this year, the patentees became aware of clerical errors in the numbering of the dependencies of claims 6, 7 and 8 and in the wording of claim 8.
6.3 During the prosecution of one of the corresponding European patent applications, it was alleged that the European no. 0 825 860 is not entitled to claim priority from British patent application no, 9508989.2 of 3 May 1995 (a copy of which is annexed hereto and marked "ACC4 "), from which the patent also claims priority. This argument could be used to attack claim 1 of the patent. The patentees however believe that the patent is fairly based on both the applications from which it claims priority, as required by section 33(2) of the Act.
6.4 But for the clerical errors referred to above, the patentees believe that the present claims of South African patent number 96/3472 are valid and enforceable. "

Further "full reasons for the amendment" are set out by the applicants as follows:

considered in the revocation application to those that are clearly being infringed and to limit their subject matter to that which is most valuable commercially. The patentees do so not because they believe that any of the claims are invalid, but out of an excess of caution and for reasons of commercial expediency.
7.2.    The patentees wish to limit the scope of the claims, thereby reducing the number of prior art documents cited against the patent in the application for revocation that need to be considered, as much of this prior art clearly falls outside the scope of the amended claims. This would lead to a reduction in the complexity of the arguments submitted in support of the validity of the patent during the hearing of the application for revocation.
7.3 The amended claims would avoid an attack based on lack of novelty and/or lack of inventive step.
7.4 The deletion of claims 7 and 8 and the correct numbering of the dependency of claim 6 removes the clerical errors in these claims. The claims are no longer open to an attack based on lack of clarity during the revocation proceedings.
7.5 The argument as to whether or not claim 1 of the patent is fairly based on the first priority application is dealt with by the proposed amendment to claim 1 as this claim is clearly
based on the first priority application, ( see page 1, lines 16 to 21, lines 28 to 32, and page 3, lines 10 to 13 of "ACC 4"). "

In terms of section 51(1) of the Act, the amendment of a patent which has been granted and is open to public inspection should be brought before the Registrar of patents, and the patentee must when filing an application for amendment set out the nature of the proposed amendment and furnish his full reasons therefor.

The present application proceedings are brought in terms of Section 51 (9) because there are revocation proceedings pending as already stated above.

Section 51 (9) provides as follows:
" Where any proceedings relating to an application for a patent or a patent are pending in any court, an application for the amendment of the relevant specification shall be made to that court, which may deal with such application for amendment as it thinks fit but subject to the provisions of sub- section(5), (6) and (7), or may stay such pending proceedings and remit such application for amendment to the Registrar to be dealt with in accordance with sub- sections (2), (3) and (4)".

An amendment of the patent that is open to public inspection is only allowable if it is not in conflict with sections 51 (6) and 51 (7) of the Act, which respectively provide as follows:
"51   (6) No amendment of a complete specification which becomes open to public inspection after the publication or the acceptance of the specification in terms of Section 42, whether before or after it so becomes open to public inspection, shall be allowed if-
(a) the effect of the amendment would be to introduce new matter or matter not in substance disclosed in the specification before amendment; or
(b) the specification as amended would include any claim not fairly based on matter disclosed in the specification before amendment. "
And

"51   (7) No amendment of a complete specification which has become open to public inspection after the publication of the acceptance of the specification in terms of section 42, shall be allowed if the specification as amended would include any claim not wholly within the scope of a claim included in the specification before the amendment. "

"4.1 The nature of the amendment is as follows:

4.1.1
The deletion of claims 2 to 5, 7 and 8, 10 to 14, 17, 18 and 20 to 25.

4.1.2

The incorporation of the subject matter of claims 2 and 4, which depend on claim 1, into claim 1 and the deletion of subject matter in claim 1 that has been replaced by the subject matter of claims 2 and 4. 4.1.3

The introduction of a concentration range of amoxicillin in mg per 5ml suspension into claim 1.

4.1.4

The introduction of the form which the medicament is to take.

4.1.5
The incorporation of the subject matter of present claims 11 and 12, which depend on claim 9, into claim 9 and the deletion of the subject matter in claim 9 that has been replaced by the subject matter of claim 11.

4.1.6
The renumbering of the remaining claims and their
dependencies.

The use of amoxycillin trihydrate and potassium clavulanate in combination, in a weight ratio of about 1. (the weights being expressed as the free parent acids amoxycillin and clavulanic acid), in the manufacture of medicament for treating bacterial infections in paediatric patients which medicament is in the form of a dry powder or granule for reconstitution into an aqueous suspensions and which contains amoxycillin in an amount offrom 150 to 450mg/5ml of such suspension twice daily (bid), at a dosage of between 40 and 70mg/kg/day of amoxycillin and pro rata amounts of clavulanic acid.
2. A use as claimed in claim 1 in which dosage regimen is 45+-10%mg/kg/day amoxycillin in combination with 6.4+-10%mg/kg/day clavulanic acid.
3. A pharmaceutical formulation adapted for paediatric oral bid administration, in the form of a dry powder or a granule formulation for reconstitution into a suspension with water or other suitable aqueous media to form a suspension formulation, comprising amoxycillin trihydrate and potassium clavulanate in combination, in a weight ratio of about 7:1 (the weights being expressed as the free parent acids amoxycillin and clavulanic acid) and which, when reconstituted, comprises amoxycillin in an amount of from 150 to 450mg/5ml of liquid aqueous suspension and clavulanic acid in an amount of from 25 to 75mg/5ml of liquid aqueous suspension.
4. A formulation as claimed in claim 3 provided for administration at a dosage offrom 40 to 70 mg/kg/day of amoxycillin.
5. A formulation as claimed in claim 3 provided for administration at a dosage of 45+-10%mg/kg/day amoxycillin and 6.4+-10%mg/kg/day clavulanic acid.
6. A formulation as claimed in any one of claims 3 to 5 provided for administration in unit doses of quantities of amoxycillin and clavulanic acid corresponding to amoxycillin : clavulanic acid ratios of 200+-10%  :  28.5+-10% and 400+-10%:  57+-10%mg/5ml."

The respondents raised grounds of opposition to the above amendment under the following captions/headings:

	

	

The basis of the respondents' opposition to the amendment herein is set out in the affidavits of one Dinesh Bheema, the respondents* addressee of the patent as follows:

Bheema, on behalf of the respondents, continues to extensively elaborate on the grounds of respondents' opposition to the amendment under the captions set out above [from pages 67-143 of the papers, vol.1]. It is not feasible to include all his arguments/criticisms in the judgement as they are voluminous, they are however fully set out in the papers, as already mentioned, and 1 have had regard to what he has stated/set out.

It suffices to state that the gist of his (Bheema's) argument as a whole is that:
�	claims 1 and 3 (read with claim 5) as sought to be amended is broader than claims 1 and 3 respectively as they exist at present and claims 1 and 3 (read with claim 5) as sought to be amended do not fall within the scope of claims included in the specifications before amendment, [in contravention of section 51(7)].

�	Certain grounds of invalidity will be present were the amendments sought in the application to be allowed.

�	The invention claimed in the patent as sought to be amended would not have been patentable [in contravention of section 61(l)(c) of the Act].

�	The invention claimed in each of the claims of the patent as sought to be amended would not be inventive [in contravention of section 25(1) of the Act].

�	Claims 1 and 3 as sought to be amended would not be clear, thus a ground for revocation.

�	The invention as exemplified in the complete specification does not lead to results and advantages set out in the complete specification, thus a ground for "inutility"/ invalidity in terms of section 61 (1 )(d) of the Act. That therefore the patent would thus be liable to revocation were the amendments to be allowed.
�	Claims 1 and 3 lack novelty and inventiveness.

�	There is no specific "disclosure" in the complete specification of a 7:1 combination of amoxycillin and clavulanate for use in children as there is in the case of adults; i.e. that integer (b) of claim 1 ["in a weight ratio of about 7:1"] and integer (d) of claim 3 ["in a weight ratio of 7:1"] are not specifically referred to in the context of the combination for children.

�	The use of a ratio of 7:1 aforesaid was not novel in the light of prior art not recited in the complete specification and clearly was not inventive given the use of the same ratio in formulations for adults.

�	The applicants have not provided "full reasons", [in contravention of section 51(1) of the Act].

�	The applicants have made themselves guilty of "culpable delay" in bringing this application and have thus acted reprehensibly and have abused the process of court.

The applicants counter these grounds of attacks (by the respondents), amongst others, through the evidence of one Anthony

�	The phrase "about 7:1 implies something at least closer to 6.5 to 7.5 to give effect to the succession of preferences, that therefore the phrase "about 7:1 includes both the 6.63:1 and the 6.68:1; and that thus there is no broadening of the scope of claim 1.

�	
�	The Applicants contend that Bheema is not an expert skilled in the art at the relevant time and therefore not competent to give evidence in so far as obviousness is concerned.
�	They deny that the documents "Dl" and "FD11" disclose all the integers of claims land 3 sought to be amended. That 'Dl' is a review article and is therefore an amalgamation of many documents, and that "FD 11" is a Patent cooperation treaty ("PCT") application that is worded very broadly. It does not disclose and/or suggest administration to children.
�	They deny that the word "about'* as sought to be introduced into claims 1 and 3 renders these claims unclear.

�	That any measures such as revised dosage regimens that can mitigate gastric intolerance would be advantageous and desirable.
White, on behalf of the applicants continues to extensively elaborate on the grounds of attack on the respondents' opposition to the amendment. It is not feasible to include all his arguments/criticisms in the judgement as they are voluminous, they are however fully set out in the papers, as already mentioned, and I have had regard to what he has stated/set out.

In legal proceedings, the modern tendency of the South African Courts lies in favour of granting the amendment of the document whenever such an amendment would facilitate the proper ventilation of the dispute. The following is stated in:

"A similar jurisprudential approach in regard to amend patent specification under the repealed Patents Act 37 of 1952 is discernable in the judgements of the South African courts. A fair reflection of that approach appears from the following dictum of Galgut J in Interfel Products (Pry) Ltd v Feltex Ltd:
T have always understood that a Court will normally be inclined to permit amendment, at least to the extent of deleting the invalid claim unless the conduct of the patentee has been such that the court in the exercise of its discretion thinks that he should be refused such relief.

Under the current Patents Act 57 of 1978 the approach of the court is no different..."

The question of which of the parties bears the onus only, of course, arises where there is a dispute to fact".

"In regard onus ofproof it was argued on behalf of the patentee that objector to the grant of an amendment is burdened with the onus in respect of all the issues which may arise in the application, while the respondent's counsel argued to the contrary. It may well be, however, that in relation to some issues the onus rests on the applicant for amendment, while in relation to others it rests on the objector. For instance, where the objection to an amendment is based on the ground of continuing invalidity of the patent, it would seem that the onus lies with the objector...but, on the other hand, where the issue is whether there has been due compliance with the statutory requirements of the application (for example as to the furnishing of full reasons 'for the amendment) and a factual dispute arises in that connection, it is arguable that the patentee bears the onus... "

On the basis of what is stated above, I am of the view that the onus is on the applicants/patentees to prove, on a balance of probabilities compliance with, amongst others, the provisions of sections 25(1), 51(1), 51(6), 51(7) and 61(1), whereas the onus is on the respondents to prove, on a balance of probabilities, amongst others, issues such as lack of novelty, lack of clarity.

Southwood J stated that:

"(9) The grant of an amendment is a discretionary matter but is subject to the provisions of ss (5), (6) and (7) of $51..."

It is important to state that in matters of this nature, it is not prudent to decide the matter without having regard to the expert evidence [on affidavit in this case].

The parties herein depended mainly on Bheema and White as the addressees of the patent respectively. Each counsel for either party argued for the acceptance of their respective expert's evidence, and in turn criticised the other.

experience in the manufacture of an antibiotic such as Amoxycillin in mixture with potassium clavulanate.

In contrast with White, on the other hand. White has intimate hands-on experience to amoxycillin/clavulanic acid since 1976; he has also advised pharmaceutical companies on development activities, studies and communication activities with respect to anti-bacterials.

What follows below summarizes some (not all) of the contentions (and criticism therof) between Bheema and White on the issues in contention herein, by way of example:

White points out that the phrase "about 7:1" is affected by what is stated in the specification and by what was commonly known by a skilled addressee in the science of compounding anti-bacterials as of the relevant priority date.

White points out that compositions such as the one protected by the patent are manufactured on an industrial scale in batches of several hundred kilograms. He points out that clavulanic acid degrades both when in storage of dry powder and in the made suspension. In order to
compensate for this degradation, an extra amount of clavulanic acid is included in the dry powder composition, typically about 8%, so that the suspension has an acceptable shelf life and when made up and after 10 days storage of suspension, still maintains a ratio within the desired limits.

He also points out that a generic company wishing to copy the product disclosed in the patent would have a product with a nominal ratio of 7:1 but in practice this may not be exactly 7:1. Such a company would have to show that their product is bio-equivalent to the originator product and in doing so, a range from 80 - 125% is generally allowed. Common sense dictates that when producing a pharmaceutical composition in large batches, it will be near impossible to archive the desired ratio with absolute accuracy, for the reasons set out above, as well as due to tolerances of the weighing equipment used during production.

Accordingly, although an addressee might aspire to produce a composition having the ratio of amoxicillin to clavulanic acid of exactly 7:1, in the industrial and the commercial arena, it is almost impossible to achieve such an exact ratio and the skilled addressee reading the specification would understand this;

The patent specification refers to numerous weight ratios namely:

Mr White's conclusion is that:
"I would therefore take the phrase 'about 7:1' to imply something at least closer to 7:1 than 6.5 - 7.5 to give effect of succession of preferences ".

And

"In my view the phrase 'about 7:1' includes both the 6.63:1 and the 6.68:1 ratios".

" With respect to paras 20 and 21, I note that claim 2 as sought to be amended is dependent upon claim 1. 1 understand this to mean that the scope of claim 2 must thereof be narrower than the scope of claim 1 and that any 'inconsistency' between the two should be decided in favour of claim 1. This is immediately achieved by the dosage of amoxicillin being limited to 45+- 10% mg/kg/day in claim 2, compared to a range of 40 -70 mg/kg/day in claim 1, without the need of any further elaboration ".

ON THE LACK OF INVENTIVENESS (OBVIOUSNESS): The legal position in this regard can be summarised as follows:
	Section 25(12), apart from an invention being "new" to qualify for the grant of a patent, also requires the invention to involve "an inventive step";

"(1). What is the inventive step said to be involved in the patent in suit?

(2).    What was, at the priority date, the state of the art (as statutorily defined) relevant to that step?

(3).    In what respect does the step go beyond, or differ from that state of the art?

(4).   Having regard to such development or difference, would the taking of the step be obvious to the skilled man? "

there is a difference but it calls for no inventive ingenuity to bring it about, there is also no subject matter; but if there is a real inventive step, no matter how small, that is sufficient to give subject matter to the patent".

It is trite that when the Court comes to consider lack of inventiveness, novelty is presumed, and, in turn, when considering novelty, inventiveness is presumed.
White disagrees with Bheema's division of intergers. According to the applicants/patentees the true integers (or parts) of the relevant claims should be:

Claim 1:
a) The use of amoxicillin trihydrate and potassium clavulanate in combination
b) In a weight ratio of about 7:1 (the weight being expressed as the free parent acids amoxicillin in clavulanic acid)
c) In the manufacture of a medicament
d) For treating bacterial infections
e) In paediatric patients
eA)Which medicament is in the form of a dry powder or granule
eA') For reconstitution into an aqueous suspension
eB) And which contains amoxicillin in an amount from 150 to 450
mg/5ml of such suspension; and
eB') Pro - rata amounts of clavulanic acid, and
f) which medicament is administered twice daily (bid)
g) At a dosage of about 40 and 70 mg/kg/day of amoxicillin, and
gA) Pro - rata amounts of clavulanic acid.

Refer White, par. 21, vol.2 pp377-378, compare Bheema par.32 vol.1 pp74-75
Claim 3
a) A pharmaceutical formulation;
b) Adapted for paediatric oral bid administration
bA) In the form of a dry powder of granule formulation
bA) For reconstitution into a suspension with water or other suitable aqueous media to form a suspension formulation
c) Comprising amoxicillin trihydrate and potassium clavulanate in combination
d) In a weight ratio of 7:1 (the weight being expressed as free parent acid amoxicillin and clavulanic acid)
e) And which, when reconstituted, comprises amoxicillin in an amount from 150 to 450 mg/5 ml of liquid aqueous suspension.
eA) clavulanic acid in an amount from 25 to 75mg/5ml of liquid aqueous suspension.

Refer White, par. 24, vol.2 pp 378 - 379; compare Bheema, par.34, vol.1 pp76-77.

Basically there is a dispute between the two addressees as to whether integers (b) of claim 3 can or cannot be used to distinguish the invention of claim 3 from an item of prior art. White argues that the language "adapted for paediatric oral bid administration" suggests to him (as an expert at the relevant time) that the formulation is specially designed, modified or made suitable for use in children rather than being a formulation that could be given to a child but is not best suited or modified for such use and that the formulation is, by its adaptation, different from, for instance a formulation intended in the main for an adult patient.

White, par. 25, vol. 2, pp 379 -380

White is of the view that Bheema should be instructing the court in so much as the art or science commonly known at the time through his own experience as a skilled addressee;

After considering all the facts before me, the legal principles/ the authorities and the arguments of all the parties , I am satisfied that on the facts before me the applicants/patentees have made out a case for the amendment. In so far as costs are concerned I am of a considered view that in the circumstances herein it will be fair, and in the interests of justice that each party pay its own costs.

In the result I make the following order:
1)	The application to amend South African Patent no. 96/3472, as set out in annexure "ACC2" of the founding papers is granted.
2)	Each party is ordered to pay its own costs.

MOLOPA-SETHOSA J